Abstract:

A nutritional supplement includes elements having been shown to enhance
DNA repair or reduce DNA damage by different molecular mechanisms while
excluding other bioactive nutrient agents which compete with any of the
elements known modes of action. The supplement includes a resveratrol, a
carotenoid, a nicotinamide, a dimethylaminoethanol, a zinc source, and a
quinic acid analog. The supplement is administered daily in dosages in
excess of normal dietary levels. The supplement improves resistance to
DNA damage, enhances DNA repair capacity in tissues including skin, and
stimulates immune cellular function. This was accomplished by reducing
metabolic competition between DNA repair bioactive components that was in
turn paralleled by enhancement of thirst quenching properties in aqueous
formulations.

Claims:

1. A nutritional supplement, comprising:at least two elements having been
shown to enhance DNA repair or reduce DNA damage by different molecular
mechanisms while excluding other bioactive nutrient agents which compete
with any of the elements known modes of action, wherein the at least two
elements are chosen from the group consisting of a resveratrol, a
carotenoid, a nicotinamide, a dimethylaminoethanol, a zinc source, and
quinic acid analog.

2. The supplement of claim 1, consisting essentially of a resveratrol, a
carotenoid, a nicotinamide, a dimethylaminoethanol, and a zinc source
wherein the supplement is essentially free of other bioactive
ingredients.

3. The supplement of claim 1, consisting essentially of a resveratrol, a
carotenoid, a nicotinamide, a dimethylaminoethanol, a zinc source, and
quinic acid analog wherein the supplement is essentially free of other
bioactive ingredients.

4. The supplement of claim 1, 2 or 3, wherein the resveratrol is a
polyphenol (e.g. 3, 5, 4'-trihydroxy-stilbene) also known as a phytolexin
or phytoestrogen that modulates cell cycle events governing growth
arrest.

5. The supplement of claim 4, wherein the resveratrol is at least between
30% to 100% pure polyphenol material.

6. The supplement of claim 1, 2 or 3, wherein the carotenoid is selected
from the group consisting of alpha carotene, beta carotene,
canthaxanthin, astaxanthin, cryptoxanthin, zeaxanthin, lutein, lycopene,
and mixtures thereof.

7. The supplement of claim 1, 2 or 3, wherein the nicotinamide is selected
from the group consisting of nicotinamide, niacin, tryptophan and
mixtures thereof.

8. The supplement of claim 1, 2 or 3, wherein the dimehtylaminoethanol
(DMAE) is selected from the group consisting of DMAE and choline analogs
that cross the blood brain barrier.

9. The supplement of claim 8, wherein the dimethylaminoethanol contains at
least 30% to 100% purity.

11. The supplement of claim 1 or 3, wherein the quinic acid analog is
selected from the group consisting of quinic acid salts, chelates, and
Uncaria water extracts.

12. The supplement of claim 1, 2, or 3, wherein the resveratrol is a
polyphenol (e.g. 3, 5, 4'-trihydroxy-stilbene) also known as a phytolexin
or phytoestrogen that modulates cell cycle events governing growth arrest
and the resveratrol is at least between 30% to 100% pure polyphenol
material, and wherein the carotenoid is selected from the group
consisting of alpha carotene, beta carotene, canthaxanthin, astaxanthin,
cryptoxanthin, zeaxanthin, lutein, lycopene, and mixtures thereof, and
wherein the nicotinamide is selected from the group consisting of
nicotinamide, niacin, tryptophan and mixtures thereof, and wherein the
dimehtylaminoethanol (DMAE) is selected from the group consisting of DMAE
and choline analogs that cross the blood brain barrier and the
dimethylaminoethanol material contains at least 30% to 100% purity,
wherein the zinc source is selected from the group consisting of zinc
sulfate, zinc salt amino acids, methionine, aspartate, dipeptides,
gluconates, halides, nitrates, oxides and acetates, and wherein the
quinic acid analog is selected from the group consisting of quinic acid
salts, chelates, and Uncaria water extracts.

14. The supplement of claim 13, wherein a dosage of the resveratrol is
about 70-2000 mg per day.

15. The supplement of claim 13, wherein a dosage of the cartenoid is about
100-200 mg per day.

16. The supplement of claim 13, wherein a dosage of the nicotinamide is
about 100-200 mg per day.

17. The supplement of claim 13, wherein a dosage of the DMAE is about
100-200 mg per day.

18. The supplement of claim 13, wherein a dosage of the zinc source is
about 10-20 mg per day.

19. The supplement of claim 13, wherein a dosage of quinic acid analog is
about 250-700 mg per day.

20. The supplement of claim 13, wherein a dosage of the resveratrol is
about 70-2000 mg per day, wherein a dosage of the cartenoid is about
100-200 mg per day, wherein a dosage of the nicotinamide is about 100-200
mg per day, wherein a dosage of the DMAE is about 100-200 mg per day,
wherein a dosage of the zinc source is about 10-20 mg per day, and
wherein a dosage of quinic acid analog is about 250-700 mg per day.

21. The supplement of claim 20, wherein the supplement is in a formulation
for oral administration.

22. The supplement of claim 20, wherein the supplement is in a formulation
for parenteral administration.

Description:

BACKGROUND OF THE INVENTION

[0001]This invention relates to novel and improved compositions for and
methods of treating humans and other animals to reduce DNA damage,
enhance DNA repair capacity, and stimulate immune cellular function. More
particularly, it relates to the administration to humans (or other
animals) a combination of resveratrol, carotenoid, nicotinamide, DMAE and
a zinc source material as a drug treatment or a daily dietary supplement,
and to compositions containing that combination of materials.

[0002]Humans have been selected over hundreds of thousands of years to
respond to not just one chemical but to a myriad of chemicals received
through the environment and mainly from one's diet. Human physiology is
extremely well balanced to handle and process these chemical mixtures to
extract as efficiently as possible the necessities of life, such as
nutritional energy sources and chemicals to maintain cellular homeostasis
and reproduction. This has to be accomplished without introducing any
toxicological consequences. Hence, it follows there is a reasonable
likelihood that when humans see natural medicines above the levels
normally found in the diet or environment, there exists a strong
interaction between the megadoses of natural medicines, so that one
supplement limits the uptake and metabolism of another, in an effort to
provide a natural selection model by which humans can be protected from
the toxicological consequences of overdosing. For example, the prior art
teaches that carotenoids and vitamins E or C are all radical
(electrophilic) scavengers and that these natural products can be
combined into supplements for additive biological effects. However,
recent literature has not confirmed this practice based on scientific
assumption because it was shown that these radical scavengers could
inhibit each other's uptake and negate the desired induction of
biological effects (Inform 6(7):778-783, 1995; Zhang et al., J. Clin.
Nutr. 62:1477 S-1482S, 1995; Niki et al., Am. J. Clin. Nutr.
62:1322S-1326S, 1995).

[0003]Selectively administering to humans, as a daily dosage, a
combination of carotenoids, nicotinamide (or niacin or a precursor
thereof) and a source of zinc, in excess of normal dietary levels, for
improving resistance to DNA damage, enhancing DNA repair capacity, and
stimulating immune function was disclosed in U.S. Pat. No. 6,020,351,
which contents are incorporated herein by reference. The term "carotenoid
material" as used herein means carotenoids, such as material selected
from the group consisting of alpha carotene, beta carotene,
canthaxanthin, lycopene and mixtures thereof. The term "nicotinamide
material" as used herein means material selected from the group
consisting of nicotinamide, niacin, tryptophan (an amino acid precursor
to niacin synthesis) and mixtures thereof. The term Dimethylaminoethanol
(DMAE) material, also called deanol, is a naturally occurring substance
that has been studied as a possible anti-aging therapy that can also
improve cognitive function. The term "zinc source material" as used
herein means an appropriate source of zinc for administration to humans
and/or other animals, e.g. one or more zinc salts, such as zinc sulfate
or other zinc salts like amino acids such as methionine or aspartate,
dipeptides, gluconates, halides, nitrates, oxides or acetates. These
ingredients have been fully described for use in treating patients having
increased DNA damage and decreased DNA repair leading to an impaired
immune function in U.S. Pat. No. 6,020,351, and also by Y Sheng, Y, Pero,
R W, Olsson, A R., Bryngelsson, C., and Hua, J M entitled "DNA Repair
Enhancement by a Combined Supplement of Carotenoids, Nicotinamide, and
Zinc" in Cancer Detection and Prevention 1998, 22(4), 284-292.

[0004]However, various commercial products so far introduced do not
establish or make obvious that any specific combinations of resveratrol,
carotenoids, nicotinamide, DMAE and zinc, which are effective at reducing
cellular DNA damage induction or enhancing DNA repair and immune function
as single agents, can also be additive or synergistic to each other in
combination. To the contrary, as demonstrated in U.S. Pat. No. 6,020,351
it was found that the administration of carotenoids, nicotinamide and
zinc, when in combination with other natural medicines or nutrients as
well, did not reduce cellular DNA damage induction or enhance DNA repair
and immune function, as had been assumed but not proven over the years in
the prior art. This observation was also consistent with the prior art
(Inform 6(7):778-783, 1995; Zhang et al., J. Clin. Nutr. 62:1477 S-1482S,
1995; Nidi et al., Am. J. Clin. Nutr. 62:1322S-1326S, 1995) which has
confirmed that carotenoids, nicotinamide and zinc in combination with
other natural products (e.g. historic medicines or nutrients) were shown
to block each other's uptake and absorption, thus resulting in altered or
metabolically blocked biological functions including DNA repair
enhancement. It follows then, although not practiced in the prior art,
that it cannot be assumed that supplementing a combination of natural
products above dietary levels will result in additive biological effects
over each product administered separately without previously establishing
they possess different modes of action to bring about a common biological
effect such as DNA repair enhancement.

[0005]Accordingly, there is a need for a combination of ingredients that
have been shown to enhance DNA repair and reduce DNA damage by different
molecular mechanisms. The present invention fulfills this need and
provides other related advantages.

SUMMARY OF THE INVENTION

[0006]The present invention involves the use of a combination supplement
consisting essentially of at least two elements having been shown to
enhance DNA repair or reduce DNA damage by different molecular mechanisms
while excluding other bioactive nutrient agents which compete with any of
the elements known modes of action. The elements comprise a resveratrol,
a carotenoid, a nicotinamide, a dimethylaminoethanol, a zinc source, and
a quinic acid analog. The resveratrol is a polyphenol (e.g. 3, 5,
4'-trihydroxy-stilbene) also known as a phytolexin or phytoestrogen that
modulates cell cycle events governing growth arrest. The resveratrol is
at least between 30% to 100% pure polyphenol material. The carotenoid is
selected from the group consisting of alpha carotene, beta carotene,
canthaxanthin, astaxanthin, cryptoxanthin, zeaxanthin, lutein, lycopene
and mixtures thereof. The nicotinamide is selected from the group
consisting of nicotinamide, niacin, tryptophan and mixtures thereof. The
dimehtylaminoethanol (DMAE) is selected from the group consisting of DMAE
and choline analogs that cross the blood brain barrier wherein the
dimethylaminoethanol contains at least 30% to 100% purity. The zinc
source is selected from the group consisting of zinc sulfate, zinc salt
amino acids, methionine, aspartate, dipeptides, gluconates, halides,
nitrates, oxides and acetates. The quinic acid analog is selected from
the group consisting of quinic acid salts, chelates, and Uncaria water
extracts.

[0007]The resveratrol, carotenoid, nicotinamide, dimehtylaminoethanol,
zinc source, and quinic acid analog are all present in proportions above
a person's normal daily dosage. A dosage of the resveratrol is about
70-2000 mg per day, the carotenoid is about 100-200 mg per day, the
nicotinamide is about 100-200 mg per day, the DMAE is about 100-200 mg
per day, the zinc source is about 10-20 mg per day, and the quinic acid
analog is about 250-700 mg per day. The supplement may be in a
formulation for oral administration or parenteral administration.

[0008]An unexpected benefit of combining non-competitive DNA repair
enhancers such as resveratrol, carotenoids, nicotinamide/niacin, DMAE and
zinc materials into anti-aging products that can synergize enhancement of
DNA repair has also been characterized as having powerful thirst
quenching properties when administered orally. The Nutra-Reservatrol
formulas of DNA enhancers are truly non-competitive in their metabolism,
because thirst quenching effects that are non-existent in most single or
other nutrient ingredients are in fact synergized to high levels of
thirst quenching abilities. Converting individual nutrient ingredients
from potentially metabolic competitive mixtures into non-competitive
Nutra-Resveratrol formulas are presented herein as biochemical evidence
that metabolic competition between Nutra-Resveratrol ingredients does not
exist, and thus are in synergized formulations evidenced by enhanced
thirst quenching.

[0009]Other features and advantages of the present invention will become
apparent from the following more detailed description, when taken in
conjunction with the accompanying drawings, which illustrate, by way of
example, the principles of the invention.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0010]The present invention is a combination supplement consisting
essentially of resveratrol, carotenoid, nicotinamide, DMAE and a zinc
source (zinc gluconate) (this combination supplement now called
Nutra-Reseratrol) over and above the normal levels of these components in
one's diet administered daily, all of which have been shown to enhance
DNA repair and reduce DNA damage by different molecular mechanisms, thus
permitting a combination of natural products having a non-competitive
activation of DNA repair having enhanced potent anti-aging properties.
The combination supplement is essentially free of other bioactive
nutrient agents that may compete with their known modes of action. The
term "bioactive nutrient agents" is employed herein as a generic
designation for vitamins, minerals and other bioactive substances serving
as anti-oxidants, anti-oxidant co-factors, or otherwise contributing to
disease prevention, inhibition of DNA damage, improvement of DNA repair
capacity, and/or enhanced immune function, such as have heretofore been
sold in concentrated, isolated, or combined form as dietary supplements
and the like for human and/or animal consumption. The combination
supplement may be embodied in formulations for oral administration, or
alternatively, in formulations for parenteral administration.

[0011]It was not obvious or practiced in the prior art that resveratrol or
DMAE could be combined with other nutritional agents known to enhance DNA
repair by avoiding metabolic competition for DNA repair enhancement. For
example, even though it has been known since 1998, there have not have
been any reports in the literature that resveratrol material also known
to be a DNA repair enhancer could be combined with carotenoid material,
nicotinamide material, DMAE material, AC-11/quinic acid material or zinc
material to create supplements that enhance DNA repair by avoiding
metabolic competition for this mode of action. Hence it was not obvious
to one skilled in the art that resveratrol could be combined with
carotenoids, nicotinamide or zinc salts to enhance DNA repair, because
they had different mechanisms of DNA repair enhancement than did
resveratrol.

[0013]The known molecular mechanisms of carotenoids are described herein.
The exact mechanism of action of carotenoids such as beta carotene is not
fully understood but it is commonly accepted scientifically that one
primary mechanism is to directly scavenge oxygen derived free radicals
produced either as by-products of metabolism or from exogenous
environmental exposures (Lieber, D. C., Ann. N.Y. Acad. Sci. 691:20-31,
1993; Bohm, F. et al., J. Photochem. Photobiol. 21(2-3):219-221, 1993;
Regnault, C. et al., Ann. Pharmacotherapy 27(11):1349-1350, 1993). As a
free radical scavenger, carotenoids can be expected to reduce or protect
against the chemical damage induced in DNA, RNA and protein of cells by
toxic environmental exposures or endogenous cellular metabolic errors
that ultimately can result in a disease state. On the other hand,
nicotinamide and zinc salts do not possess this chemical property which
results in an improved biological cellular function.

[0014]The known molecular mechanisms of nicotinamide are described herein.
Nicotinamide and its metabolic equivalent nicotinic acid (niacin, vitamin
B) or even tryptophan which is the synthetic precursor to niacin is the
main precursor for the formation and maintenance of the cellular pool of
NAD (Bernofsky, Mol. Cell. Biochem. 33:135-143, 1980; Olsson, A. et al.,
Biochem. Pharmacol. 45:1191-1200, 1993). NAD is essential for cellular
ATP production and maintenance of the cell's redox potential, and it is
also the substrate for the DNA repair enzyme, poly ADP-ribosyl
transferase (ADPRT). Niacin deprivation decreases the NAD pools
significantly both in tissue culture cells (Jacobson, E. et al., IN:
ADP-Ribosylation Reactions (Poirier, G. G. and Moreau, P., eds.), pp.
153-162, Springer Verlag, New York, N.Y., 1992), and animal systems
(Zhang et al., J. Nutri. 123:1349-1355, 1993) as well as humans (Fu et
al., J. Nutri. 119:1949-1955, 1989). The depleted cells have an increased
sensitivity to DNA damage and the levels of poly (ADP-ribose) production
in cultured cells (Jacobson, E. L., as cited, 1992) or in rat liver
(Rawling et al., J. Nutri. 124:1597-1603, 1994) were significantly lower
after mild nicotinamide deficiency. On the other hand, when niacin was
given as a supplement to ordinary nutrition (i.e. above known dietary
levels) the NAD pool increased and the cells were less sensitive to
oxygen radicals (Weitberg, A. B., Mutational Res. 216:197-201, 1989).
Therefore, it is obvious from this review of the prior art that the
primary mechanism of action of nicotinamide/niacin differs from
carotenoids and zinc in that the cell's potential for energy metabolism
is increased by amplifying NAD and ATP pool supplies (i.e. these
biochemicals are the energy sources of living organisms) which in turn is
useful to cells, tissues and organs to reduce DNA damage, enhance DNA
repair (i.e. poly ADP-ribosylation) and stimulate immune function where
the relevance to the disease state is apparent (Pero, R. W. et al.,
Biochimie 77:385-393, 1995).

[0015]The known molecular mechanisms of DMAE material is described herein.
Dimethylaminoethanol (DMAE) material, also known as deanol, is a
naturally occurring substance that has been studied as a possible
anti-ageing therapy that can also improve cognitive function, reduce
neurological stress, improves immunity and DNA repair especially in skin.
It is the precursor to choline and may increase acetylcholine levels
(Grossman R. The role of dimethylaminoethanol in cosmetic dermatology. Am
J Clin Dermatol 6:39-47, 2005). While choline is known to be the
precursor of acetylcholine, a recognized neurotransmitter, DMAE may also
prove to offer a more direct approach to this function by moving into the
brain, being acted on by an enzyme (methylation), and thereby undergoing
conversion into choline directly where it is needed. DMAE inhibits
production of the age-related pigment lipofuscin, which accumulates in
all aging tissues. This is significant because cells with increased
lipofuscin cause lysosomes to perform poorly, which leads to increased
accumulation of poorly functioning mitochondria and increased reactive
oxygen species (ROS) production (Terman A, Brunk U T. Oxidative stress,
accumulation of biological "garbage," and aging. Antioxid Redox Signal
8(1-2):197-204, 2006:). Evidence also suggests that DMAE decreases the
extent of crosslinking of proteins possibly by acting as a free-radical
scavenger (Nagy I, Nagy K. On the role of cross-linking of cellular
proteins in aging. Mech Ageing Dev 14(1-2):245-251, 1980).

[0017]Resveratrol material is defined herein as a polyphenol (e.g. 3, 5,
4'-trihydroxy-stilbene) that can induce cell cycle arrest thereby
permitting greater opportunities to remove DNA damage by DNA repair, and
thus stimulate normal cell survival and longevity, which in turn can also
result in an increased immune cell function (Dario R. Valenzano et al.,
Current Biology 16 (3): 296-300, 2006; Feng Y H et al. Acta Pharmacol Sin
2002 10: 893-897, 2002; Susanne and rea Gatz et al. Carcinogenesis 2008
29(3):519-527). These properties for resveratrol materials were not known
at the time carotenoid-nicotinamide-zinc materials were described for
their non-competitive modes of action in 2000 that directly related to
the mechanisms of DNA damage and its repair in U.S. Pat. No. 6,020,151.
Thus, this is a novel discovery adding to the previous scientific
knowledge already cited.

[0019]In addition, a water extract of Cat's Claw (Uncaria species) called
AC-11 or its active ingredient quinic acid analogs are also DNA repair
enhancers that do not metabolically compete with resveratrol material,
carotenoid material, nicotinamide material, DMAE material or zinc
material, and as such could be added to the DNA repair mixture without
inducing metabolic competition and thus inhibiting DNA repair instead of
being synergist, because the mode of action of AC-11/quinic acid to
increasing DNA repair is novel to inducing DNA repair by increasing
uptake of urinary tryptophan and nicotinamide (Pero et al Phytotherapy
Res 23:335-346, 2009, Pero et al Current Clinical Pharmacology 5: 67-73,
2010).

[0021]In summation, even though resveratrol, carotenoids,
nicotinamide/niacin, DMAE and zinc have been shown to have some enabling
utility in cell and animal models as single agents in the prevention of
certain diseases and in the stimulation of immune function and DNA
repair, there has been a lack of corresponding, consistent data in humans
(Bodgen, J. D. et al., Amer. J. Clin. Nutri. 48:655-663, 1988; Walsh, C.
T. et al., Environmental Health Perspectives 102(Suppl. 2):5-46, 1994;
Dario R. Valenzano et al. Current Biology 16 (3): 296-300, 2006). In
addition, it is not possible for one skilled in the art to predict
whether agents with different mechanisms of action will be synergistic or
additive to the biological response they will elicit when given in
combination. However, the prior art as described and shown in U.S. Pat.
No. 6,202,351 does teach that non-competitive molecular mechanisms that
enhance DNA repair will at least be additive to each other.

[0022]In addition, quite remarkably and an unexpected benefit of combining
non-competitive DNA repair enhancers such as resveratrol, carotenoids,
nicotinamide/niacin, DMAE and zinc materials into anti-aging products
that can synergize enhancement of DNA repair has also been characterized
as having powerful thirst quenching properties when administered orally.
Since this property has never been observed before for the aforementioned
DNA repair enhancers when administered previously as single agents, then
this observation becomes unique and proprietary to this patent
application. It also supports that the Nutra-Reseratrol formulas (i.e.
combinations of resveratrol, carotenoids, nicotinamide/niacin, DMAE and
zinc materials) are indeed non-competitive metabolic mixtures, because
otherwise they would not synergize their thirst quenching effects in
parallel if these effects were also competitive.

[0023]The design of the study to prove this invention was based on
combining substances with known properties to prevent cancer, stimulate
immune function and enhance DNA repair, but with differing mechanisms of
action that they did not compete with each other; e.g. combinations of
resveratrol=cell cycle modulation, carotenoids=electrophilic scavenger of
radicals produced endogenously by cells or exogenously by the
environment, nicotinamide=amplified source of energy via increased
production of NAD or ATP, DMAE=improved mitochrondial function and
zinc=an essential cofactor to antioxidant, replicative and DNA repair
enzymes in cells.

[0024]The hypothesis was that since none of these DNA repair inducing
substances have produced consistent effects in humans as a single
administered agent, this shortcoming might be overcome if administered in
specific combination, because these substances might produce a
consistently additive or synergistic chemo-preventive biological
response. This could be true if their mechanisms of action were
non-competitive, and thus not inhibiting each other's effects being
induced on DNA repair. Here we provide the evidence that
Nutra-Reservatrol formulas of DNA repair enhancers are truly
non-competitive in their metabolism, because thirst quenching effects
that are non-existent in most single or other nutrient ingredients are in
fact synergized to high levels of thirst quenching abilities. Converting
individual nutrient ingredients from potentially metabolic competitive
mixtures into non-competitive Nutra-Resveratrol formulas when in
combination are determined and presented here, as biochemical evidence
that metabolic competition between Nutra-Resveratrol ingredients does not
exist, and thus are in synergized formulations evidenced by enhanced
thirst quenching.

[0025]In illustrative or preferred practice of the invention, the
resveratrol material may be selected from the group consisting of 3, 5,
4'-trihydroxy-stilbene or an equivalent polyphenol in pure or extract
form; the carotenoid material may be selected from the group consisting
of alpha carotene, beta carotene, canthaxanthin, lycopene and mixtures
thereof; the nicotinamide material may be selected from the group
consisting of nicotinamide, niacin, tryptophan and mixtures thereof; the
DMAE material may be selected from a group consisting of other choline
analogs that pass the blood brain barrier and the zinc source material
may be one or more zinc salts.

[0026]For human administration, the resveratrol material, carotenoid
material, nicotinamide material, DMAE material and zinc source material
may be present in proportions effective, in combination, to improve
resistance to DNA damage, enhance DNA repair capacity, and stimulate
immune function in a human subject to whom the composition is
administered as a daily dosage.

[0027]The invention also contemplates the provision of a method of
treating a human or other animal subject, consisting of administering
resveratrol material, carotenoid material, nicotinamide material, DMAE
material and zinc source material to the subject to selectively
supplement the subject's dietary intake thereof (i.e., without
supplementing the dietary intake of any other active nutrient agents
having competing modes of action) and repeating the administration on a
substantially daily basis.

[0028]Thus, in a particular sense, the invention contemplates the
provision of a method of treating a human subject consisting of
selectively administering to the subject resveratrol, carotenoid,
nicotinamide, DMAE and a zinc source in daily dosage amounts effective,
in combination, to improve resistance to DNA damage, enhance DNA repair
capacity, and stimulate immune function. In a specific example of
currently preferred dosage range for humans, about 100-2000 mg
resveratrol, about 100 mg of carotenoid, about 100 mg of nicotinamide,
about 100 mg DMAE, and about 10 mg of a zinc source are administered
daily in this method.

[0029]From a theoretical standpoint, this invention is based on a
principle of combining chemical products which are individually known to
possess either cancer preventive or immune stimulatory properties into
one formulation which contains only active components where at least one
mechanism of action for each active component is known to be different
from the known mechanisms of action of the other components to stimulate
DNA repair. So far as applicant is aware, this particular combination of
ingredients has not heretofore been recognized in the art.

[0030]The invention involves the discovery that natural products should
not be combined into a natural medicine unless one tests whether each
ingredient is additive to the overall desired biological effect, and that
one way to accomplish this endpoint is to not combine natural products
that have similar modes of action and thus competitive routes of
absorption and excretion without first testing the combination for
additive effects. That is to say, the present invention avoids inhibited
uptake and absorption of natural products, thereby obtaining additive
biological effects, by combining only natural products having well
defined different and thus potentially non-competitive modes of action
which is, for example, the case with the exclusive combination of
resveratrol, carotenoids, nicotinamide, DMAE, and zinc.

[0031]The practice of this invention involves supplementing humans or
animals for example, by the oral, intraperitoneal, intravenous,
subcutaneous or intramuscular routes of administration with the
combination of resveratrol, carotenoids, nicotinamide/niacin, DMAE and an
appropriate zinc salt at a dose of this combination that exceeds a normal
dietary supplementation. The practice of the prior art teaches that
dietary supplementation containing this combination together with
simultaneous supplementation of other nutrients and/or natural products
cannot enhance immune function (Payette, H. et al., Am. J. Clin. Nutr.
52:927-932, 1990; Zhang et al., J. Clin. Nutr. 62:1477 S-1482S, 1995;
U.S. Pat. No. 6,020,351) but when resveratrol, carotenoids (as Caroplex,
C.E. Jamieson, Ltd., Ontario, Canada), nicotinamide, DMAE and a zinc salt
are given alone in the absence of other natural supplements above dietary
levels, e.g. 70-2000 mg per day, 100 mg per day, 100 mg per day, 100 mg
per day and 10 mg per day by oral daily administration, respectively, the
resistance to oxidative cellular DNA damage, and enhancement of DNA
repair and immune function were observed.

[0032]The clinical evaluation in a previous study (U.S. Pat. No.
6,020,351) was determined by comparing each individual's biological
response before and after supplementation. In such a manner, each
individual became his own control; e.g. the male subjects were given
baseline measurements of resistance to cellular DNA damage, enhancement
of DNA repair and stimulation of immune function once a week for 4 weeks,
and then they were supplemented daily and the same measurements repeated
once a week for the last 5 weeks of a 7 week intervention period. The
before measurements (i.e. n=4) were the baseline biological response
parameters to be compared to the after measurements (i.e. n=5). One
individual was not supplemented to provide a control for the supplemented
individuals. The data from this experimental design has taught that
resistance to cellular DNA damage, enhancement of DNA repair and
stimulation of immune function were all significantly modulated by a
combination of carotenoids, nicotinamide, and zinc when administered as
an exclusive drug combination above dietary levels, but not when
co-administered together with other additional nutrient or natural
product supplements.

[0033]The following examples (Tables 1-5) are some preferred features but
not limitations to this invention. The compositions of DNA repair
enhancers presented herein contain both well-known bioactive DNA repair
components as well as inert ingredients pertinent to beverage
formulations rendering the products favorable for smell, taste, color,
viscosity and water solubility. Whereas the so-called inert ingredients
do not necessarily vary from one formulation to another, it is sometimes
highly desirable to vary the bioactive ingredients of formulations to
achieve high specificity and duration of biological responses. As already
mentioned, the DNA repair ingredients may vary in amounts (doses) from
one formulation to another in Tables 1-5, e.g. resveratrol=0.07 gm to 2.0
gm per 1000 gm water, carotenoids=0.01 gm to 0.3 gm per 1000 gm water,
nicotinamide=0.01 gm to 0.3 gm per 1000 gm water, DMAE=0.01 gm to 0.3 gm
per 1000 gm water, or Zinc=0.001 gm to 0.03 gm per 1000 gm water.

[0034]The total sample size for each evaluation was 3 fluid ounces (about
90 ml): i.e. after this consumption there is no more can be supplied.
Each subject consumes a 1 2×2 inch saline cracker (Nabisco Original
Saltine Crackers) before tasting each new product identified as products
#A (Minute Maid Lemonade), #B (Nutra-Resveratrol Lemon Lime), #C
(Gatorade), #D (Nutra-Resveratrol Orange Mango), or #E (Poland Spring
Water). After the saline and first tasting the self-report clinical
examination form is filled out for ranking of thirst quenching only
(Table 2), and in addition as influenced by taste, appearance and smell
of the products (Table 3) according to the scale provided of 1=worst
ranking, 2, 3, 4, 5=best ranking. The subject is instructed to first rank
all products for thirst quenching, and then repeat the process also
taking into consideration taste, smell and appearance of the products.
Once the subject has decided sample ranking the data are then compared to
water (#E). Ranked Values greater than water (#E) are considered to have
an improved thirst quenching ability over water alone.

[0035]Below is a sample summary data sheet for all self-reported clinical
examinations used for final analysis.

[0037]Evaluation of thirst quenching together with taste, smell, and
appearance by comparison of the following products according to the self
report clinical examination forms: Minute Maid Lemonade,
Nutra-Reservatrol lemon lime, Gatorade, Nutra-Resveratrol orange mango,
Polan Spring water. The data sheets for self-report clinical examinations
used here, equally rank thirst quenching only from 1-5, and together with
taste, appearance and smell from 1-5, and then report the sum of these
two assessments as the final score herein. The composition of
Nutra-Resveratrol lemon lime or orange mango flavors can be found in
Table 1. Lemonade Minute Maid, Gatorade and Water Poland Spring are
commercial products where their ingredients are defined publicly on every
can or bottle sold. As such they are among the best examples of thirst
quenchers already being sold to the public.

[0038]In conclusion, Tables 7 and 8 have presented data demonstrating that
Nutra-Resveratrol ingredients (Tables 1-5) which are characterized as DNA
repair mixtures of resveratrol, carotenoid, nicotinamide, DMAE, and zinc
gluconate that do not metabolically compete with each other because they
modulate DNA repair by different molecular mechanisms that in turn
achieve an additive or synergistic effect. Biochemical evidence is
presented in Tables 7 and 8 because individual Nutra-Resveratrol
ingredients have never been shown to have thirst quenching effects.
However, when they are combined in non-competitive mixtures, there is
also parallel metabolic synergy of other biochemical properties such as
enhanced thirst quenching) (Tables 7-8).

[0039]Moreover, when Nutra-Resveratrol formulas or other commercial thirst
quenchers, such as lemonade or Gatorade, were directly compared to water
they all were more effective, scoring between 32.4% to 45.9% higher than
water as shown on Table 7. This was true even in taste, appearance, and
smell were also taken into consideration being 29.4% to 69.1% better than
water (Table 8).

[0040]All the thirst quenching formulas were positively influenced (i.e.
increased) by their formulations when compared to water except
Nutra-Resveratrol orange mango which did not increase its thirst
quenching value (Tables 2-3). Apparently Nutra-Resveratrol orange mango
was not a preferred formulation mixture when considering taste,
appearance and smell for these DNA repairs.

[0041]The role of calories and sugars in DNA repair synergized formulas
with thirst quenching properties compared to commercial beverages and
water was also looked at. It is striking how different Gatorade and
lemonade are from Nutra-Resveratrol formulas in regard to calories and
sugar content (see Table 9 below).

[0042]First of all, Nutra-Resveratrol mixtures were formulated as
anti-aging beverages having enhanced DNA repair health benefits, whereas
Gatorade and lemonade only have dehydration and thirst quenching health
benefits. Reducing calories from 50-100 per serving as it is with
Gatorade and lemonade to 10 per serving as it is in Nutra-Resveratrol
formulas is in itself a large health benefit, since weight gain is a
potent inducer of bad health. To achieve this added benefit, and yet
still have both anti-aging and thirst quenching properties as in the
Nutra-Resveratrol formulas, has to be considered a very favorable
development and not predicted by the scientific prior art.

[0043]All the thirst quenching formulas tested also had sugars present in
their formulas (Table 9). The commercial products (Gatorade and lemonade)
had much higher levels of 14-27 gm per serving compared to 2 gm per
serving for the Nutra-Resveratrol formulas tested. Sugars in general are
also an unhealthy source to stimulate any beneficial nutritional
metabolism. Although sugars may enhance thirst quenching properties as
evidenced by the data presented in Tables 7-8, they are questionable
ingredients adding no further health benefit beyond preventing
dehydration.

[0044]Although several embodiments have been described in detail for
purposes of illustration, various modifications may be made to each
without departing from the scope and spirit of the invention.
Accordingly, the invention is not to be limited, except as by the
appended claims.